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TERATOGENIC RESPONSES OF TGFALPHA KNOCKOUT FETUSES TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)
Citation:
Abbott, B D., A R. Buckalew, AND P. L. Bryant. TERATOGENIC RESPONSES OF TGFALPHA KNOCKOUT FETUSES TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD). Presented at Teratology Society Meeting, Montreal, Quebec, Canada, June 23-28, 2001.
Description:
ABBOTT1, B.D., A.R. BUCKALEW1, and P.L. BRYANT2. 1Reproductive Toxicology Division, EPA, RAP, NC; 2Dept. Environ. Sciences & Engineering, UNC, Chapel Hill, NC. Teratogenic responses of TGF knockout fetuses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
TCDD induces cleft palate and hydronephrosis in C57BL/6N mice and an oral dose of 24 ?g TCDD/kg results in high incidences of both defects without maternal or fetal lethality. These effects correlate with altered expression of the epidermal growth factor (EGF) receptor and its ligands, EGF and transforming growth factor alpha (TGF ). The present study examines the role of TGF in the teratogenic responses. Pregnant TGF knockout mice (C57BL/6J strain background) were dosed orally on GD12 with corn oil, 1, 5, 10, or 24 ?g TCDD/kg. On GD17.5, maternal and fetal body weight, liver and placental weights, litter size, cleft palate and hydronephrosis were evaluated. Renal pelvic space dilation was scored from 0-4 and scores of 2 or higher were considered hydronephrotic. Maternal, fetal and placental weights, maternal weight gain and fetal survival were not affected by treatment. Maternal and fetal relative and absolute liver weights significantly increased in TCDD-exposed animals. Fetuses exposed to TCDD developed severe hydronephrosis and at all dose levels 100% of the fetuses were affected with mean severity scores ranging from 3.48 to 3.91. This is a more severe response than that reported for similarly exposed wild type C57BL/6N fetuses, suggesting that absence of TGF enhances the sensitivity of the urinary tract to TCDD. Vehicle exposed TGF null fetuses had enlarged renal pelvic spaces (mean score 1.62?0.07) and this may contribute to the severity of the response. TGF KO fetuses exposed to 5 ?g TCDD /kg or higher had cleft palate and the dose-related incidence appeared similar to that reported for C57BL/6N TCDD-exposed fetuses. In conclusion, the expression of TGF is not required for induction of cleft palate or hydronephrosis. However there may be some modulatory or protective effect of this growth factor, as the responses appeared more severe in its absence. : This abstract does not necessarily reflect EPA policy.